Treatment of therapy-resistant Sézary syndrome with Cyclosporin-A: suppression of pruritus, leukaemic T cell activation markers and tumour mass.

A patient with Sézary's syndrome resistant to conventional therapy was successfully treated with Cyclosporin-A (CyA) for 14 months. Pre-treatment in vitro studies showed that the leukaemic T cells were sensitive to therapeutic concentrations of CyA. The patient's pruritus disappeared promptly after 2 d of treatment. The positive effect of CyA on the pruritus was related to the dose and plasma concentrations of the drug. Analysis of leukaemic cell surface markers using monoclonal antibodies showed that episodes of pruritus were correlated with the appearance of cells expressing the T cell "activation" markers interferon- gamma (IFN-gamma) and HLA-DR. This indicated that CyA may control pruritus by suppressing the production/release of lymphokines. Immunohistochemical staining of repeated skin biopsies demonstrated a reduction of infiltrating T cells. Clinically, this was correlated with an improved skin status and a partial regress of palpable lymph node size. Apart from an initial reversible drop in the circulating helper/suppressor T cell ratio, the number of circulating Sézary cells was unaltered during CyA treatment. After 5 months, higher doses of CyA were needed to control symptoms, and this was correlated wit with partial drug resistance also in vitro.